Beyond melanoma, pembrolizumab is also being tested
in clinical trials as a potential treatment for more than 30
other types of cancer. Results are not yet available for the
majority of these. However, early results show that the
immunotherapeutic bene;ts some patients with NSCLC
and, potentially, some with head and neck cancer (114,

115), although these results are preliminary.

A second therapeutic antibody targeting PD- 1, nivolumab,
is also being tested in clinical trials as a potential treatment
for numerous cancer types. Recent preliminary results
show that nivolumab bene;ts some patients with advanced
melanoma; it has been reported that more than 40 percent
of patients are still gaining bene;t from this therapeutic
more than three years a;er starting treatment (116). Early
results indicate that it may also bene;t patients with NSCLC
(117, 118), Hodgkin lymphoma, and renal cell carcinoma
(119), which is the most common form of kidney cancer.

Recent promising early results from a small clinical trial
showed that a therapeutic that targets PD-L1, MPDL3280A,
could bene;t patients with bladder cancer (120). As a result,
the FDA granted MPDL3280A breakthrough designation
for the treatment of bladder cancer.

Unfortunately, not all patients have dramatic responses
following treatment with ipilimumab or a PD1-targeted
therapeutic. To help increase the number of patients who
may bene;t from these therapeutics, researchers are assessing
combinations of immunotherapeutics that target di;erent
checkpoint proteins and combinations of immunotherapeutics
that work in di;erent ways, as well as combining
immunotherapeutics with other types of anticancer treatments,
including molecularly targeted therapeutics.

To this end, recent remarkable results showed that 75percent of patients with metastatic melanoma treatedwith a combination of ipilimumab and nivolumab werestill bene;ting two years a;er the start of treatment(121). In a second small clinical trial, early results showedthat a combination of ipilimumab and an oncolyticvirotherapeutic called talimogene laherparepvec bene;tedmore patients with metastatic melanoma than eitherimmunotherapeutic alone (122).

Enhancing the Killing Power of the Immune System

Another approach to cancer immunotherapy is to boost
the ability of T cells to eliminate cancer cells. To return to
the analogy of the car, this approach is like stepping on the
accelerator, and it can be achieved in a number of ways,
including the administration of adoptive T-cell therapy, a
soluble molecule called a cytokine that can enhance T cell
function, or a therapeutic cancer vaccine.

Adoptive T-cell therapies are complex medical procedures
built upon our accumulating knowledge of the biology
of cancer and the biology of the immune system. In
these procedures, T cells are harvested from a patient,
expanded in number and/or genetically modi;ed in
the laboratory, and then returned to the patient, where
they attack and potentially eliminate the cancer cells. No
FDA-approved adoptive T-cell therapies are yet available.
Several approaches, however, are currently being tested for
a number of types of cancer, one of which, called CTL019,
recently received breakthrough therapy designation from
the FDA for the treatment of ALL (see sidebar on Types of

Adoptive T-Cell Therapies). No treatment
advances

for bladder cancer have been
made in nearly 30 years despite
it being the ninth most common
cancer worldwide.